ARNI or ARB Treats Residual Left Ventricular Remodelling after Surgery for Valvular Regurgitation: ReReRe study protocol

AIMS: Patients with persistent or de novo left ventricular (LV) dilation and/or reduced ejection fraction (EF) after correction for primary aortic (AR) or mitral (MR) regurgitation (i.e. residual LV remodelling) have not been well studied with regard to guideline‐directed medical therapy after successful aetiology‐reversing surgery. We aim to (i) compare the effectiveness of sacubitril/valsartan vs. valsartan in promoting LV reverse remodelling and (ii) explore the safety of medication withdrawal after LV recovery. METHODS AND RESULTS: The ReReRe study is a multicentre, randomized, open‐label, parallel trial that consists of two consecutive parts. A total of 371 patients with an LV end‐diastolic diameter (LVEDD) > 60 mm or LVEF < 50%, assessed by transthoracic echocardiography (TTE) 7–14 days after valve surgery for significant AR or primary MR will be enrolled. The 1(st) randomization into the sacubitril/valsartan or valsartan groups and structured follow‐up (1, 3, 6, 9, and 12 months after randomization) will be conducted to observe the primary objective as the rate of complete recovery of LV remodelling (i.e. LVEDD < 55 mm and LVEF ≥ 60% by TTE at two consecutive visits). Those who have complete recovery of LV remodelling will be enrolled in Study Part 2; consequently, they will receive the 2(nd) randomization into the medication withdrawal or maintenance group and 6‐monthly visits for the observation of the primary objective as the rate of LV remodelling relapse (LVEDD > 60 mm or LVEF < 50%). The secondary objectives include the rate of composite clinical outcomes and the degree of change in 6‐min walk distance and Kansas City Cardiomyopathy Questionnaire scores. CONCLUSIONS: The ReReRe study will provide new evidence for the treatment of patients with residual LV remodelling after curable unloaded surgery, as well as the duration of treatment. The study results will fill the gap in identifying an appropriate medical therapy regimen for this group of patients and perhaps for those with reversible aetiologies of heart failure.